This project involves studies on the isolation, the biochemical mechanisms of action, and metabolic fate of antitumor agents derived from plants. Several plants of reputed antitumor activity are to be assayed for inhibition of the growth of murine tumor cell lines. Active agents will be extracted from such plants and purified by methods such as chromatography, gel filtration and crystallization. Identification would be made, if possible, by elemental analysis, molecular weight determinations, spectroscopy and chemical reactivity. For both these new agents, and for many more currently used drugs such as the vinca alkaloids, the colchicine derivatives and the antitumor antibiotics, efforts will be made to elucidate as far as is possible their mechanism of action and metabolic fate. This will be undertaken with whole cells, isolated enzymes and intact animals. Biochemical pathways will be assayed in most cases using radioactive precursors. Uptake of tritium labeled drugs will also be studied. Spectral shifts and Tm changes, dialysis and gel filtration will be used to study drug interactions with high molecular weight material. Thinlayer, paper and column chromatography will be the major tools for studying drug metabolism.